Molecular Mechanisms of Antibody-Mediated Rejection and Accommodation in Organ Transplantation

Author:

Kenta Iwasaki,Takaaki Kobayashi

Abstract

Antibody-mediated rejection (ABMR) in organ transplantation has been recognized as the main cause of graft rejection. Binding of donor-specific HLA antibody (DSA) and A/B blood type antibody on graft endothelial cells causes complement-dependent tissue damage. C4d, a product of the complement cascade, has long been an indicator of graft tissue damage in graft endothelial cells. By contrast, recent evidences indicated histological findings of ABMR without C4d deposition in many cases and Banff classification criteria included a category of C4d-negative ABMR. Several mechanisms have been proposed for complement-independent tissue injury in the presence of DSA. It is well known that activated monocytes and macrophages infiltrate into graft tissues. The inflammatory environment triggered by the binding of DSA to endothelial cells alone can induce an allo-reaction of CD4 T-cells via graft endothelial cell HLA-class II. Accommodation is a condition that no rejections occur even in the presence of an antibody against donor organs and becomes attracting considerable attention as a therapeutic strategy to acquire long-term survival of the transplanted organs. Several recent publications have suggested some mechanistic insights about graft accommodation, including the upregulation of antioxidant, anti-apoptotic, and complement regulatory proteins genes via activation of PI3K/AKT survival signal or inactivation of extracellular signal-regulated protein kinase pro-inflammatory signals after DSA and anti-A/B antibody ligation on endothelial cells.

Publisher

S. Karger AG

Reference28 articles.

1. Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, et al. The Banff 2017 kidney meeting report: revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018;18(2):293–307.

2. Tatapudi VS, Montgomery RA. Therapeutic modulation of the complement system in kidney transplantation: clinical indications and emerging drug leads. Front Immunol. 2019;10:2306.

3. Haas M. The significance of C4d staining with minimal histologic abnormalities. Curr Opin Organ Transplant. 2010;15(1):21–7.

4. Nagelkerke SQ, Kuijpers TW. Immunomodulation by IVIg and the role of Fc-gamma receptors: classic mechanisms of action after all? Front Immunol. 2015;5:674.

5. Das LK, Ide K, Tanaka A, Morimoto H, Shimizu S, Tanimine N, et al. Fc-gamma receptor 3A polymorphism predicts the incidence of urinary tract infection in kidney-transplant recipients. Hum Immunol. 2017;78(4):357–62.

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